Phase 4
Completed N=20
A Pharmacokinetics, Pharmacodynamics and Safety Study of Warfarin in Combination With Tamiflu (Oseltamivir)
Drug Therapy, Combination
Source: ClinicalTrials.gov NCT02780622 ↗
Enrolled (actual)
20
Serious AEs
2.5%
Results posted
Sep 2016
Primary outcomePrimary: Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for International Normalized Ratio (INR) — -2.16; -9.06 hours*ratio
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
Summary
This is an open-label, randomized, 2-period crossover study, to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of warfarin in combination with Tamiflu (oseltamivir) in participants stabilized on warfarin. Participants will be randomized to receive either their warfarin followed oseltamivir and warfarin, or by oseltamivir and warfarin followed by warfarin. The treatment periods will be separated by a washout period of at least 4 days. Participants will continue receiving warfarin once daily at a prescribed usual dose throughout the study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for International Normalized Ratio (INR) |
-2.16; -9.06 | — |
| PRIMARY Change From Baseline in Maximum Observed Effect (Emax) of International Normalized Ratio (INR) |
0.3; 0.1 | — |
| PRIMARY Time to Reach Maximum Change From Baseline in International Normalized Ratio (INR) (Tmax) |
24.00; 0.00 | — |
| PRIMARY Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for Factor VII Activity |
0.568; 1.45 | — |
| PRIMARY Change From Baseline in Maximum Observed Effect (Emax) in Factor VII Activity |
-0.0505; -0.0432 | — |
| PRIMARY Time to Reach Maximum Change From Baseline in Factor VII Activity (Tmax) |
96.00; 72.00 | — |
| PRIMARY Change From Baseline in Plasma Concentration of Vitamin K1 |
305; 271 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate |
0.50; 4.00; 0.75; 4.00 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin |
2.00; 4.00; 14.5; 3.01; 3.00; 4.00 | — |
| SECONDARY Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate |
1.77; 6.17; 4.00; 8.19 | — |
| SECONDARY Terminal Half-life (t½) for R- and S- Warfarin |
45.4; 45.6; 56.1; 53.6 | — |
| SECONDARY Oral Plasma Clearance (CL/F) for Oseltamivir |
558; 463 | — |
| SECONDARY Oral Plasma Clearance (CL/F) for R- and S- Warfarin |
0.198; 0.208; 38.5; 38.2; 0.139; 0.145 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate |
88.9; 367; 91.2; 571 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) for R- and S- Warfarin |
394; 330; 1.87; 1.68; 436; 375 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for Oseltamivir and Oseltamivir Carboxylate |
176; 7180 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin |
6770; 6460; 35.2; 33.9; 7790; 7360 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate |
141; 2990; 169; 5110 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin |
3610; 3380; 18.6; 17.8; 4140; 3870 | — |
| SECONDARY Percentage of Participants With Adverse Events |
25.0; 25.0 | — |
Eligibility Criteria
Inclusion Criteria
- Participants must have been receiving warfarin once daily for at least 4 weeks prior to Screening
- Participants must have regular International Normalized ratio (INR) monitoring during warfarin therapy prior to study entry, and be willing to be trained in the use of CoaguCheck devices
- INR must fall within a target range of 2.0-3.5
- Body mass index (BMI) between 18-32 kg/m^2 inclusive
Exclusion Criteria
- An INR value between screening and Day -1 lower than 2.0 or greater than 3.5
- A change in prescribed daily warfarin dose between Screening and Day -1
- History of any coagulopathy
- Consumption of health products or supplements containing vitamin K
- Pregnant or lactating women
- Confirmed positive urine and/or blood test for drugs of abuse at Screening or Day -1
Data sourced from ClinicalTrials.gov (NCT02780622). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.